This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Betterle, C. Articles by Presotto, F. Search for Related Content PubMed PubMed Citation Articles by Betterle, C. Articles by Presotto, F.

I. Adrenal Cortex and Steroid 21-Hydroxylase Autoantibodies in Adult Patients with Organ-Specific Autoimmune Diseases: Markers of Low Progression to Clinical Addison’s Disease

Chair of Clinical Immunology and Allergy (C.B., M.V., B.P., F.P.), and Chair of Endocrinology (M.B.) from the Institute of Semeiotica Medica; Department of Pediatrics (N.A.G.), University of Padova, Padova; Chair of Immunology (F.T.), Institute of General Pathology, University of Trieste; Department of Laboratory Medicine, Padova General Hospital (M.S.), Padova, Italy; FIRS Laboratories (B.R.S., J.F., S.C.), RSR Ltd, Parc Ty Glas, Llanishen, Cardiff CF4 5DU and Department of Medicine, University of Wales, College of Medicine, Heath Park, Cardiff CF4 4XN, United Kingdom

Address all correspondence and requests for reprints to: Professor Corrado Betterle, Istituto di Semeiotica Medica, Cattedra di Immunologia Clinica e Allergologia, Università di Padova, Via Ospedale 105, 35128 - Padova, Italy.

Adrenal cortex antibodies (ACA) were measured by immunofluorescence in 8840 adult patients with organ-specific autoimmune diseases without overt hypoadrenalism. Sixty-seven (0.8%) patients were ACA-positive, with the highest prevalence in those with premature ovarian failure (8.9%). Forty-eight ACA-positive and 20 ACA-negative individuals were enrolled into a prospective study. Antibodies to steroid 21-hydroxylase (21-OH), steroid 17-hydroxylase (17-OH) and cytochrome P450 side chain cleavage enzyme (P450scc) were measured by immunoprecipitation assay. Human leucocyte antigens D-related (HLA-DR) genotyping was also carried out and adrenal function assessed by ACTH test. On enrollment, 75% of ACA-positive patients had a normal adrenal function, while 25% revealed a subclinical hypoadrenalism. 21-OH antibodies were positive in 91% of ACA-positive sera. Eleven patients were positive for steroid-cell antibodies by immunofluorescence, and 9 revealed a positivity for antibodies to 17-OH and/or P450scc. During the prospective study, overt Addison’s disease developed in 21% and subclinical hypoadrenalism in 29% of ACA-positive patients, while 50% maintained normal adrenal function. Progression to Addison’s disease was more frequent in patients with subclinical hypoadrenalism, high titers of ACA and higher levels of 21-OH antibodies, complement-fixing ACA and HLA-DR3 status. All 20 persistently ACA-negative patients were also negative for antibodies to 21-OH, 17-OH, and P450scc, and all maintained normal adrenal function during follow-up. In conclusion, the detection of ACA/21-OH antibodies in adults is a marker of low progression toward clinical Addison’s disease. .

This article has been cited by other articles:

				L. M. Nelson Primary Ovarian Insufficiency N. Engl. J. Med., February 5, 2009; 360(6): 606 - 614. [Full Text] [PDF]

				S. Hassler, C. Ramsey, M. C. Karlsson, D. Larsson, B. Herrmann, B. Rozell, M. Backheden, L. Peltonen, O. Kampe, and O. Winqvist Aire-deficient mice develop hematopoetic irregularities and marginal zone B-cell lymphoma Blood, September 15, 2006; 108(6): 1941 - 1948. [Abstract] [Full Text] [PDF]

				R. Giordano, M. Balbo, A. Picu, L. Bonelli, R. Berardelli, A. Falorni, E. Ghigo, and E. Arvat Corticotrope hypersecretion coupled with cortisol hypo-responsiveness to stimuli is present in patients with autoimmune endocrine diseases: evidence for subclinical primary hypoadrenalism? Eur. J. Endocrinol., September 1, 2006; 155(3): 421 - 428. [Abstract] [Full Text] [PDF]

				G. Coco, C. Dal Pra, F. Presotto, M. P. Albergoni, C. Canova, B. Pedini, R. Zanchetta, S. Chen, J. Furmaniak, B. Rees Smith, et al. Estimated Risk for Developing Autoimmune Addison's Disease in Patients with Adrenal Cortex Autoantibodies J. Clin. Endocrinol. Metab., May 1, 2006; 91(5): 1637 - 1645. [Abstract] [Full Text] [PDF]

				C. K. Welt, A. Falorni, A. E. Taylor, K. A. Martin, and J. E. Hall Selective Theca Cell Dysfunction in Autoimmune Oophoritis Results in Multifollicular Development, Decreased Estradiol, and Elevated Inhibin B Levels J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 3069 - 3076. [Abstract] [Full Text] [PDF]

				A. Falorni, S. Laureti, A. De Bellis, R. Zanchetta, C. Tiberti, G. Arnaldi, V. Bini, P. Beck-Peccoz, A. Bizzarro, F. Dotta, et al. Italian Addison Network Study: Update of Diagnostic Criteria for the Etiological Classification of Primary Adrenal Insufficiency J. Clin. Endocrinol. Metab., April 1, 2004; 89(4): 1598 - 1604. [Abstract] [Full Text] [PDF]

				S. H. S. Pearce and N. J. Leech Toward Precise Forecasting of Autoimmune Endocrinopathy J. Clin. Endocrinol. Metab., February 1, 2004; 89(2): 544 - 547. [Full Text] [PDF]

				R. Giordano, M. Pellegrino, S. Oleandri, M. Baldi, M. Balbo, S. Laureti, A. Falorni, E. Ghigo, and E. Arvat Adrenal Sensitivity to Adrenocorticotropin 1-24 Is Reduced in Patients with Autoimmune Polyglandular Syndrome J. Clin. Endocrinol. Metab., February 1, 2004; 89(2): 675 - 680. [Abstract] [Full Text] [PDF]

				V.K. Bakalov, V.H. Vanderhoof, C.A. Bondy, and L.M. Nelson Adrenal antibodies detect asymptomatic auto-immune adrenal insufficiency in young women with spontaneous premature ovarian failure Hum. Reprod., August 1, 2002; 17(8): 2096 - 2100. [Abstract] [Full Text] [PDF]

				C. Betterle, C. Dal Pra, F. Mantero, and R. Zanchetta Autoimmune Adrenal Insufficiency and Autoimmune Polyendocrine Syndromes: Autoantibodies, Autoantigens, and Their Applicability in Diagnosis and Disease Prediction Endocr. Rev., June 1, 2002; 23(3): 327 - 364. [Abstract] [Full Text] [PDF]

				A. G. Myhre, D. E. Undlien, K. Lovas, S. Uhlving, B. G. Nedrebo, K. J. Fougner, T. Trovik, J. I. Sorheim, and E. S. Husebye Autoimmune Adrenocortical Failure in Norway Autoantibodies and Human Leukocyte Antigen Class II Associations Related to Clinical Features J. Clin. Endocrinol. Metab., February 1, 2002; 87(2): 618 - 623. [Abstract] [Full Text] [PDF]

				A. De Bellis, A. Falorni, S. Laureti, S. Perrino, C. Coronella, F. Forini, E. Bizzarro, A. Bizzarro, G. Abbate, and A. Bellastella Time Course of 21-Hydroxylase Antibodies and Long-Term Remission of Subclinical Autoimmune Adrenalitis after Corticosteroid Therapy: Case Report J. Clin. Endocrinol. Metab., February 1, 2001; 86(2): 675 - 678. [Abstract] [Full Text]

				C. Jaeger, E. Hatziagelaki, R. Petzoldt, and R. G. Bretzel Comparative Analysis of Organ-Specific Autoantibodies and Celiac Disease--Associated Antibodies in Type 1 Diabetic Patients, Their First-Degree Relatives, and Healthy Control Subjects Diabetes Care, January 1, 2001; 24(1): 27 - 32. [Abstract] [Full Text]

				G. Gambelunghe, A. Falorni, M. Ghaderi, S. Laureti, C. Tortoioli, F. Santeusanio, P. Brunetti, and C. B. Sanjeevi Microsatellite Polymorphism of the MHC Class I Chain-Related (MIC-A and MIC-B) Genes Marks the Risk for Autoimmune Addison's Disease J. Clin. Endocrinol. Metab., October 1, 1999; 84(10): 3701 - 3707. [Abstract] [Full Text] [PDF]

				L. Yu, K. W. Brewer, S. Gates, A. Wu, T. Wang, S. R. Babu, P. A. Gottlieb, B. M. Freed, J. Noble, H. A. Erlich, et al. DRB104 and DQ Alleles: Expression of 21-Hydroxylase Autoantibodies and Risk of Progression to Addison's Disease J. Clin. Endocrinol. Metab., January 1, 1999; 84(1): 328 - 335. [Abstract] [Full Text]

				S. Laureti, A. De Bellis, V. I. Muccitelli, F. Calcinaro, A. Bizzarro, R. Rossi, A. Bellastella, F. Santeusanio, and A. Falorni Levels of Adrenocortical Autoantibodies Correlate with the Degree of Adrenal Dysfunction in Subjects with Preclinical Addison's Disease J. Clin. Endocrinol. Metab., October 1, 1998; 83(10): 3507 - 3511. [Abstract] [Full Text]

				S. Chen, J. Sawicka, L. Prentice, J. F. Sanders, H. Tanaka, V. Petersen, C. Betterle, M. Volpato, S. Roberts, M. Powell, et al. Analysis of Autoantibody Epitopes on Steroid 21-Hydroxylase Using a Panel of Monoclonal Antibodies J. Clin. Endocrinol. Metab., August 1, 1998; 83(8): 2977 - 2986. [Abstract] [Full Text]

				C. Betterle, N. A. Greggio, and M. Volpato Autoimmune Polyglandular Syndrome Type 1 J. Clin. Endocrinol. Metab., April 1, 1998; 83(4): 1049 - 1055. [Full Text]

				H. Tanaka, M. S. Perez, M. Powell, J. F. Sanders, J. Sawicka, S. Chen, L. Prentice, T. Asawa, C. Betterle, M. Volpato, et al. Steroid 21-Hydroxylase Autoantibodies: Measurements with a New Immunoprecipitation Assay J. Clin. Endocrinol. Metab., May 1, 1997; 82(5): 1440 - 1446. [Abstract] [Full Text] [PDF]